Action Points

Note that there was a signiﬁcantly increased risk of death in the 25- to 44-year age group.

Compared with those younger and older, people between 25 and 75 have the greatest risk of death and adverse cardiovascular events in the short- and long-term following a first-time syncope episode, a population-based study found.

Otherwise healthy individuals between 26 and 44 years who had a first-time episode of syncope had the highest risk of mortality at 1 year (HR 2.02), followed by the 45- to 74-year-age group (HR 1.29) when adjusted for sex, age, comorbidity, and pharmacotherapy (P<0.0001 for both when compared with controls), according to Martin Ruwald, MD, of Copenhagen University Hospital in Denmark, and colleagues.

When followed for a median 4.5 years, the same younger age group (26-44) was found to have the greatest risk for longer-term death (HR 2.29 versus 1.23 for ages 45-74, P<0.0001 for both when compared with controls), researchers reported online in the Journal of American College of Cardiology.

"This is important new information not previously shown in larger studies," Ruwald and colleagues wrote regarding the finding of increased risk among those 26 to 44 years old.

They hypothesized that there may be unrecognized cardiovascular disease in this age group causing a worse prognosis.

"It may not be safe to rely on a history of no comorbidity when evaluating a patient with syncope, as some studies suggest," they wrote.

Ruwald and colleagues used the Danish National Patient Register to identify 37,017 healthy individuals with a first-time admission to a hospital or emergency department for syncope between Jan. 1, 2001, and Dec. 31, 2009. They were matched by age and sex with 185,085 controls from the Danish population.

The mean follow-up was 4.5 years, the median age was 47 years, and 53% were women. The population was studied over all ages as well as by separate age groups: <25, 26 to 44, 45 to 74, and >75 years.

The primary outcomes were 1-year and long-term mortality. The secondary outcomes were insertion of an implantable cardioverter-defibrillator (ICD) or pacemaker, stroke, cardiovascular hospitalization, and admission for recurrent syncope.

The overall 1-year mortality rate was 1.9% in the syncope group versus 2% in the control group, a nonsignificant difference across all ages, but significantly increased in the 25 to 74 age group (P<0.0001).

The overall long-term mortality rate was 8.2% in the syncope group versus 7.7% in controls, conferring a 6% increased risk for the syncope group (HR 1.06, 95% CI 1.02 to 1.10, P=0.0033). However, the significance was lost for those under 25 and over 75.

The syncope group also had an increased risk for cardiovascular comorbidities in the long-term analysis including increased number of hospitalizations for cardiovascular disease (HR 1.74), ICD or pacemaker implantations (HR 5.52), and stroke (HR 1.35), which were all highly significant at P<0.0001.

The overall event rate for recurrent syncope was very high (45 per 1,000 person-years), confirmed in the multivariable adjusted Cox regression analysis. In addition, all age groups had a highly significant increased risk of recurrent syncope, with the greatest risk being for those between ages 26 and 44.

"However, the event rate, in numbers not previously seen, describes very well what is observed by clinicians, that the syncope patient is seen in hospital several times and most likely is submitted to several tests, which have low diagnostic yield," investigators said.

In a commentary, Robert Sheldon, MD, PhD, of the Libin Cardiovascular Institute of Alberta, Canada, noted that the study was significant for its ability to examine a large group of low-risk patients.

While the overall risk of death was low, he stressed that every patient still needs to be carefully reviewed especially with the increased risk seen in the middle age group, particularly those between 26 and 44. He also agreed that this highlights the need for better risk-stratification tools as syncope consumed $2.4 billion in healthcare costs in the U.S. in 2003, equal to asthma.

The strengths of this paper include a long follow-up period and large sample size. Also, using a nationwide database minimizes the risk of selection bias.

The limitations of this study, according to the authors, include that it is an observational study and there is a lack of key data including cause of death, electrocardiograms, and additional hospital studies, which can also provide significant prognostic information. Finally, although it is a large sample size, the population was from a single country, questioning the generalizability.

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.